calcium/calmodulin dependent protein kinase 2

Function

• prominent kinase in the central nervous system
• the major protein of post-synaptic densities
• may function in long-term potentiation (LTP) & neurotransmitter release
• member of the NMDA receptor (NMDAR) signaling complex in excitatory synapses
• may regulate NMDAR-dependent potentiation of the AMPAR & synaptic plasticity (putative)

 CaM kinase II substrates include 14-3-3 beta                           Ser60, Ser65 AMPA receptors Adenylyl Cyclase olfactory AC3        Ser1076 Calpain II                            RGS*TAGGCR Calponin                              Ser175 cAMP phosphodiesterase CDC25C Choline Acetyl Transferase CPI 17                                Ser 130, Thr 38 Chromogranin A (bovine) CREB                                  Ser142 Dihydropteridine reductase Dystrophin eNOS                                  Ser1117 ErbB2                                 Thr1172 FLIP GABA A receptor, beta 1               Ser384, Ser409 GABA A receptor, gamma 2              Ser348, Ser350 GluR1 AMPA receptor subunit           Ser831, Ser845 Histamine H1 receptor Heat Shock Factor 1                   Ser230 Homer 1b Insulin receptor substrate 58kDA Internexin alpha Kv1.4 channel MAP-2 Myogenic factor SRF                   Ser103, Thr160 D-Myo-inositol 1,4,5 3P3 kinase       Thr311 Myosin non muscle form                Thr1940 NBP60 Neurofilament L                       Ser57 NMDA receptor subunit NR2B            Ser1303 nNOS                                  Ser847 PSD95/SAP90 PSD95 associated protein PEA-15                                Ser116 Phosducin                             Ser54, Ser73 Phospholamban                         Thr17 Phospholipase C beta 3                Ser537 Rabphilin 3A                          Ser34, Thr205,Thr209 Raf-1 RAP (receptor assoc. protein) RF-C replication factor C large subunit Ribosomal protein S18 Ryanodine Receptor (cardiac)         Ser2809 & others SAP97 Sepiapterin reductase Stat1                                 Ser727 Stathmin                              Ser16 Synapsin 1 Tau                                   Ser262, Ser365 Tiam1 TNF-receptor associated protein TOAD-64 Troponin T                            Ser190 (bovine) tubulin alpha tubulin beta Tyrosine Hydroxylase                  Ser19 VAMP/synaptobrevin (SYB) Vanilloid receptor 1                  Ser502, Thr 704

Structure

• multiple (28) isoforms encoded by four genes: alpha, beta, delta, gamma
• different isoforms assemble into homo- or heteromultimeric holoenzymes composed of 8 to 12 subunits
• basic structure of each isoform consists of
  • catalytic domain
  • autoinhibitory or regulatory domain
  • variable segment
  • self-association domain

Compartment

• cell junction, synapse
• presynaptic cell membrane (putative)
• postsynaptic lipid rafts (putative)

Expression

• highly expressed in brain, constituting 1-2% of total protein; alpha & beta subunits are predominant

More general terms

• multisubunit protein
• Ca+2/calmodulin-dependent protein kinase (CaM kinase)
• calmodulin binding protein
• PEST protein

Additional terms

• Ca+2/calmodulin-dependent protein kinase II gamma (CAMK2G, CAMKG)
• calcium-calmodulin-dependent protein kinase II activity in serum
• calcium/calmodulin-dependent protein kinase II delta (CAMK2D)